An in vitro model to determine the mechanism of induction of rheumatic heart disease is being developed. The mechanism of induction of rheumatic heart disease will be studied with culture embryonic cardiac myofibers as target cells for "sensitized" lymphocytes to determine the role of delayed hypersensitivity and antibody in rheumatic fever. Lymphocytes obtained from experimental animals sensitized to various purified streptococcal antigens are being tested. The cytotoxic effects of these cells will be studied by various chemical and immunological methods applicable to tissue culture techniques. It is hoped that the cardiac target cell reaction may be used to establish a specific streptococcal antigen as the "rheumatogenic" agent. M proteins from group A streptococci obtained from upper respiratory and pyodermal infections are being studied with respect to antigenic specificity, techniques of purification, primary and tertiary structures, as related to cross-reactions among serotypes and responses in immunized animals. Secretory antibody specific for streptococcal M proteins is being investigated with respect to mechanisms of protection in upper respiratory infection.